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UDC: 616.5-004:616.5-007.23:615.262:615.355
ENZYME PREPARATION IN THERAPY FOR LICHEN SCLEROSIS IN THE FEMALE EXTERNAL GENITAL ORGANS
Altai State Medical University, Barnaul Yu.S. Kondratyeva, S.O. Filinova
The article presents literature data on lichen sclerosis localized in female external genital organs. There are described the mesh, disease pathogenesis, features of clinical forms, given modern treatment regimens. There are obtained the results of clinical observation and treatment of lichen, sclerosis of external genital organs, with the "use" enzyme in the form of preparation. The data obtained allow for recommend the state-of-the-treatment of lichen sclerosiss in the processes area in the women. Key Word: Lichen sclerosis, genital forms, diagnostics, treatment.
Lichen sclerosis (lichen sclerosus et atrophicus) is a slow onset chronic disease with the visible atrophy of skin and mucous membrane, often localized in the area of female genitals[1].
The disease is of scientific and clinical interest, since an increasing number of patients with lichen sclerosis (LS) is being registered in all countries, and the occurrence of a significant number of cases in girls and women of different ages is of interest to specialists in the clinic, diagnostics and treatment of this pathology [1-4].
LS was firstly described in 1889 by French dermatologist F. H. Hallopeau, (1842-1919) [1]. Noso-logical identity of LS is not clearly defined, however, most authors consider the disease as a kind of superficial scleroderma, some as a variant of lichen ruber planus [1, 2, 4, 5, 6]. Grebennikov V.A. and Chilimova RA (1983) indicated that in lichen sclerosis, in contrast to the atrophic form of the red flat lichen, there is no itching in the disease sites [5]. Some authors consider lichen sclerosis as an independent disease that occupies an intermediate position between the scleroderma and lichen ruber pla-nus, and when localized on genitals it is identified with Kraurosis vulvae [7]. In foreign literature, LS is considered an independent nosological entity [4-6, 8]. Women are exposed to the disease 4-10 times more often than men [3]. Lichen sclerosis can be combined with typical signs of lichen ruber pla-nus and scleroderma lesions. There are described cases of combination with systemic scleroderma [1]. According to foreign researchers, by the localization of LS on the genital organs, the process can be complicated by the development of squamous cell carcinoma [5]. Carlietal P. et al. (2003) observed the association for lichen sclerosis with squamous cell carcinoma against the background of papillo-maviral infection [6].
The exact cause of LS is unknown. A number of factors that may be involved in the development of the disease have been examined. In particular, genetic factors: clear link with the family medical history, family cases of LS registered between twins, sisters, mother and daughter
and according to the researchers, the development of LS and its degree of severity were connected with the inheritance of a number of genes [7].
Extragenital LS is often combined with mor-phea, which leads to conclusions about common pathomechanism of these diseases [7]. According to foreign studies, 67 percent of patients with LS showed low titer autoantibodies against the protein extracellular molecule 1 (ESM-1) and collagen XII, resulting in the conclusion of autoimmune disease pathogenesis [9]. Sometimes the progression of LS is associated with local skin damage. The trigger for the progression of LS can be an injury in the area of old scars, radiation exposure of the skin with radiotherapy, roughness, chronic skin irritation with urine in patients with diabetes mellitus [9] Some authors note neuroendocrine mechanisms of the progression of the disease, in particular, dishormonal changes in the pituitary gland- adrenal glands-ovary [8]. Most of the time, LS is observed in girls in the puberty, which may be associated with the low level of estrogen, as a result of later periods of puberty, menstrual dysfunction. Also, the lichen sclerosis process develops against the background of endocrine disorders associated with aging and cessation of the reproductive functions of the body. In women who are in menopausal and post-menopausal periods, the disease manifests itself as a lesion of the vulva and periproctic zone, and takes a persistent recurrent character, resulting in vulvar dystrophy [1]. In the pathogenesis of these disorders, inflammatory diseases of the pelvic organs, an insufficient estrogen level, progesterone and other hormones involved in the synthesis of collagen and other connective tissue components, microcirculation disorder , elasticity and tone of peripheral vessels are important.
The main complaints of LS patients with external genital organs are skin changes, feeling of re-densification, tightness, numbness, itching, pain, dysuria, and sexual contacts become painful [3]. The disease sites can be single or multiple, have different shapes-rounded, oval, linear, anoma-
lous, and color- depending on disease state, from bright pink to white yellowish sheen. The surface of the lesion has waxy luster, the peripheral zone is cyanotic. Depending on the stage of the pathological process, the phenomena of induration or atrophy can be made. All these phenomena, in addition to unpleasant subjective esthesia, cause patients considerable moral suffering and significantly diminish the quality of their lives, as they are a serious cosmetic defect.
Eruptions tend to spontaneous resolution, leaving atrophic hypopigmented or amelanotic spots. The disease sites of the genitals can be isolated and characterized by a wide variety of clinical manifestations [7]. The following clinical varieties of genital lichen sclerosis are distinguished: papular, erythematous-edematic, vitiligine, bullous, atrophic and erosive-ulcerative form. Quite often lichen sclerosis of vulva turns into kraurosis vul-vae, which is characterized by the progression of sclerosis and loss of tissue mobility, subjectively kraurosis vulvae is accompanied by intense itching
[7].
The pathomorphological picture of LS is represented by the atrophy of the epidermis, hyperker-atotic with follicular plugs, and hydropic degeneration of the basal layer. In the dermis, directly under the epidermis, there is edema with the ho-mogenization of gelatinous fibers, under which there is a tramline infiltrate from lymphocytes with an admixture of histiocytes. With a bullous form, a bubble forms in the edema zone, and the infiltration diminished in intensity [7].
The main goal of LS therapy is to slow the progression of the disease, to achieve stabilization of the process, and then regress the clinical picture, so treatment should be timely, multi-component and pathogenetically justified. Considering the probability of development of cicatricial deformity of the mucous genital organs in patients, the analysis of clinical manifestations, outcomes and active search for effective methods of treatment is carried out.
Three pathogenetic links determine the range of curative interventions for the treatment of genital injuries in the case of lesion scleroderma and LS: excessive fibrotic formation, a violation of microcirculation and immune disorders. Currently, anti-bacterial drugs of the penicillin group are used in the therapy of LS: benzylpenicillin, penicilla-mine (fusidic acid, oxacillin sodium, ampicillin, amoxicillin are used for intolerance), enzymes (li-dase, trypsin, chymotrypsin, solcoseryl, hyaluro-nidases), vasoactive agent (trental, pentoxifylline, xantinol nicotinate), vitamins A, E, B, D2, nicotinic acid. Glucocorticoid ointments, also solcoseryl, actovegin, methyluracil ointments are applied externally to the disease sites . In a subacute stage, physiotherapeutic procedures are prescribed: ultrasound , sonic phoresis, phonophoresis with
lidase, photophoresis, electrophoresis , thermal procedures (paraffinotherapy, peloid , diathermy ), balneotherapy [9, 10, 11, 12]. A number of modern medicines have the ability to act simultaneously at many pathogenetic links of the LS. These medicines are lon-gidaza, which belongs to the group of enzymatic drugs. The combination therapy of plaque sclero-derma includes the usage of longidaza in the form of a solution 3000 IU for intramuscular injection [13, 14]. Due to the peculiarities of the blood supply and innervation of the external genital organs, the stabilization and resolution of the process occurs in the form of a reduction in the local inflammatory pattern, indurative manifestations, trophic disturbances from the medial vulva to lateral areas, and a gradual decrease in itching, burning sensations from the lateral areas to the clitoral and the anterior commissure [12, 13]. The results of biochemical and immunological, histological studies indicate that longidaza does not damage ordinal connective tissue, does not have a teratogenic and carcinogenic effect [14]. Experimental study of the pharmacokinetics of suppositories revealed that the drug is distributed at high speed throughout the body, absorbed well into the bloodstream and reaches a maximum concentration in the blood after 1 hour, with a characteristic lack of tissue cumulation. The elimination half-life is 42 to 84 hours. Bioavailability of longidaza suppositories is at least 70% [14]. When prescribed in combination with other drugs, the possibility of increasing their bioavailability and enhancing systemic action should be considered.
We have the clinical experience of using longi-daza suppositories in therapy of patients with LS.
Materials and methods
At the Department of Dermatovenereology, Cosmetology and Immunology, Altai State Medical University, 16 women were diagnosed with a diagnosis of LS of external genital organs. The age of the patient ranged from 30 to 65 years. The duration of the disease ranged from 2 to 15 years.
Patients at circulation noted the following complaints: skin changes in the genital area were observed in 15 women (93, 75%), 8 women (50%) noted the feeling of redensification of the skin and mucous external genital organs, a feeling of tightness and numbness disturbed the same number of patients - 8 women (50%), itching was present in 10 patients (62.5%), discomfort and soreness in sexual intercourse - 5 women (31.25%). At the same time, 2 patients (12.5%) had localization of LS lesions on the skin.
In studying the medical history of life, concomitant somatic diseases were noted: 10 women (62,5%) had bronchopulmonary diseases: acute respiratory diseases- tonsillitis- 6 women (37.5%), strep throat- 4 women (25%); also there was a pathology of the endocrine system: 3 women (18.75%)
had hypothyroidism and 1 woman (6.25%) had diabetes mellitus. There were 5 women in menopause (31.25%).
The clinical picture in patients was represented by similar symptoms- multiple and / or single lesions, depending on the disease state with varying degrees of color, atrophy and sclerosis. All of the patients received treatment: anti-infectives of the penicillin, vasoprotective (pentoxifylline, xantinol nicotinate), drugs that improve microcirculation and have reparative properties (actovegin, solcoseryl), vitamin and microelement complexes. All women in the combination therapy were prescribed an enzyme preparation of longidaza 3000 IU vaginally once in 2 days - 10 suppositories. External therapy included the usage of topical glu-cocorticoids of weak activity in combination with actovegin or solcoseryl.
The effectiveness of treatment after 1 month was evaluated according to the following clinical score: the dynamics of the pathological process, taking into account the local inflammatory pattern, inducible manifestations and trophic disorders (discoloration, decreased dryness of the mucocutaneous membranes, the disappearance of inflammatory infiltration and epithelialization of cracks), as well as the reduction or disappearance of itching and burning sensation. The dynamics of the clinical picture are reflected in Figure 1. After the treatment, such clinical signs as inflammatory infiltration, itching, burning sensation were completely stopped in all women, dry skin and mucous membranes were preserved in 2 women (12.5%), the appearance of new cracks was observed in only 2 patients (12.5% ).
100 90 80 70 60 50 40 30 20 10 0
93,75
12,5
Dryness of cutaneomucosal membranes
68,75
Inflammatory infiltration
62,5
0
Itching
50
31,25
112,5 ■
Burning sensation Appearance of new cracks
I Before treatment ■ After treatment
0
0
Figure 1.
Clinical features of the LS of the external genital organs
Results and discussion
Clinical observation 1. Patient M., 52 years old, considers herself ill for 12 years, when she first discovered the appearance of spots on the skin of the breast, and then after 4 years she noticed excessive dryness and cracks in the large and small vulvar lip, accompanied by itching, discoloration and structure change of the skin. The gynecologist diagnosed the following: The vulva-vaginal candi-diasis. The treatment assigned did not have a positive dynamic. From medical history: Physiological menopause from 43 years. Of the comorbid condition- idiopathic hypertension, hypothyroidism, medically compensated.
St.localis: The pathological process is widespread and localized on the skin of the chest, in the area
of the external genital organs with the transition to the periproctic zone. There are several lesions up to 3 cm in diameter, oval in shape and indurated in the brilliantly white colored central part on the skin of the chest. The disease sites of the skin of the external genital organs in the form of sclerosis sites with radial folding of tissues, depigment-ed spots, cracks, bleeding painful erosions amid hyperemia and atrophy. Also around the affected areas was a pale pink bezel. There were initial signs of stenosis of the vagina. The zone of the atrophic process had the outlines of the "eight" or the shape of the "sand-glass". Subjectively, the patient was troubled by itching, burning sensation, painful urination and dryness of mucous of EGP (external genital pore). The following diagnose was given:
Lichen sclerosis of the skin and external genital organs, erosive-helcoid form. Fixed treatment course: Benzylpenicillin novocainic salt in 600 thousand. Unit I.M. 2 times per day - 20 days, trental endo-venous drip No.10, AEvit 1 capsule 3 times a day, suppositories of longidaza 3000 IU vaginally 10 administrations every other day, alternating with suppositories triozhenal No. 10. Apply externaly on the rash ointment solcoseryl and hydrocortisone cream 1%. At the end of therapy, complaints of itching, burning sensation does not note. Clinically, the decrease in the phenomena of atrophy and xerosis, the healing of cracks. After 2 months after treatment, full epithelization of erosions, a decrease in the phenomena of atrophy and sclerosis, the cessation of the appearance of new cracks, the pain symptomatic is stopped.
Clinical observation 2. Patient E., 47 years old, is sick for 3 years, when she first discovered skin changes in the field of EGP, she was not treated, she did not consult doctors. From medical history: a condition of a perimenopause, from accompanying diseases: Diabetes mellitus 2 type.
St.localis:on the external genital organs with the transition to the perianal zone, the perineum, areas of atrophy of whitish color against the background of hyperemia and edema of the labia ma-joria are noted. Subjectively, the patient was bothered by the itching and dryness of mucous EGP, dyspareunia. Diagnosed with: Lichen sclerosis of external genital organs, erythematic form. Fixed the course of outpatient medicine: trental 100 mg 3 times a day 1 month, AEvit 1 capsule 3 times a day, ebastine 10 mg 1 time a day 14 days, suppositories longidaza 3000 IU vaginally 10 administrations every other day, externally- methyluracil ointment and hydrocortisone cream 1%. At the end of the course of therapy, subjective complaints are not noted. In the inspection, reduction of the phenomena of xerosis, atrophy, erythema.
Analyzing all of the above, we can speak about the effectiveness and expediency of combination treatment with the inclusion in the therapy scheme women with atrophic diseases of the external genital organs of the enzyme preparation of longidaza 3000 IU in the form of suppositories. The use of this treatment regimens in our observation allowed us to stop completely inflammatory infiltration, itching, burning sensation in all patients, to reduce the dryness of the cutaneomucosal, and the appearance of new cracks.
Conclusion
Thus, the described changes and the presented clinical examples demonstrate the need for a more careful approach, consultation and treatment of these patients together with gynecologists, en-docrinologists. Existing pathological processes in the field of external genital organs in women, of course, cause significant moral suffering to pa-
tients and significantly diminish the quality of their lives, which must be remembered when counseling and treating patients with this pathology.
Список литературы
1. Grebennikov V.A., Chilimova R.A. Transformation of scleroatrophic liena into systemic scleroderma. Vestnik Dermatologii i Venerologii. 1983; 1(4): 60-63.
2. Kryazheva S.S., Boldyreva M.V. Telangiectatic form of sclerotrophic silicium. Russian Journal of Skin and Venereal Diseases. 1999; 1(6): 27—29.
3. Dermatology: Atlas-reference book: Trans. from eng.: Practice. 1999.
4. ВгассоG. L.etal. Clinical and histologic effects of topical treatments of vulvar lichen sclero-sus. Acriticalevaluation. J. Reprod. Med. 1993; 38: 37.
5. Chalmers R. J. G. et al. Lichen sclerosus et atrophicus: a common and distinctive cause of phimosis in boys. Arch. Dermatol. 1984; 120: 1025— 1027.
6. Friedrich E. G., Kalra P. S. Serum levels of sex hormones in vulvar lichen sclerosus and the effect of topical testosterone. N. Engl. J. Med. 1984; 310: 488—491.
7. Private dermatology: Medicine. 1965.
8. Chfrles C., Clements P., Furst D. Systemic sclerosis: hypothesis-driven treatment strategis. The Lancet. 2006; 367(9523): 1683-91.
9. Klaus Wolf, Lowell A. Goldmitt, Stephen and Kate, etc. Fifcpatrick's dermatology in clinical practice: in 3 volumes. trans. from the English; Izda-telstvo Panfilova: BINOM. Knowledge laboratory; 2012.
10. Nikitina M.N., Oreshkina Yu.I., Grishko T.N. Focal scleroderma of external genital organs. Vestnik Dermatologii i Venerologii. 1983; 8: 39-43.
11. Kulagin V.I., Markina Ye. I. Etiology and pathogenesis of sclerotrophic lichen. Russian Journal of Skin and Venereal Diseases. 2003; 1(2):51-52.
12. Sherman V, McPherson T, Baldo M, Salim A, Gao XH, Wojnarowska F. The high rate of familial lichen sclerosus suggests a genetic contribution: an observational cohort study. J EurAcadDermatol-Venereol. 2010.
13. Scleroderma: Textbook. 2002.
14. Vidal reference book: medicines in Russia. Moscow: UBM Medica Rus; 2014.
Contacts
Corresponding author: Kondratyeva Yulia Serge-yevna, Doctor of medical Sciences, Associate Professor, Head of the Department of dermatovene-reology, cosmetology and immunology of ASMU, Barnaul.
656038, Barnaul, Lenina Prospekt, 40. Tel.: (3852) 554578. E-mail: julia_jsk@mail.ru
